Abstract 3539: Indoleamine-2,3-dioxygenase 2 (IDO-2) is expressed in hepatoblastoma cells and associated with metastatic state
Authors: Lisandro Luques, Ashby Kissoondoyal, Emily De Sousa, Paula Quaglietta, David Malkin, Stefano Cairo, Emilie Indersie, Reto Baertschiger
Journal: Cancer Research (2023)

Abstract Hepatoblastoma (HB) is the most common pediatric primary liver malignancy and represents about 1% of all pediatric tumors. Incidence of HB has been increasing in the past 10 years. Risk stratification of HB patients is established by the extent of the liver disease, patient age, levels of serum AFP and presence of metastatic disease. Currently, treatment and prognosis of HB patients relies on chemotherapy and complete tumor resection. Unfortunately, patients with high-risk HB (metastatic, unresectable, refractory and recurrent) have dismal prognosis. The molecular mechanisms underlying the aggressiveness and metastatic potential of the tumor have not been elucidated yet. Tryptophan-2,3-dioxygenase (TDO) and indoleamine-2,3-dioxygenase 1 and 2 (IDO 1 and IDO-2) are enzymes in mammals that catabolize tryptophan to kynurenine and its activity has been related with immunoregulation and tumorigenesis. While TDO and IDO-1 have been extensively studied before the discovery of IDO-2, the role of the later in tumorigenesis is still under evaluation. Expression of IDO-2 is normally found in liver, kidney, pancreas, brain and epididymis while a dysregulated expression was reported in different types of cancer. IDO-2 activity was found to affect both the immune cells activation status and also the proliferation, migration and survival of tumor cells both in vitro and in vivo. Despite being expressed in normal liver tissues, IDO-2 expression has never been assessed in HB cells. The aim of this study was to determine if IDO-2 mRNA is expressed in HB cell lines and to determine if this expression is correlated with patient risk classification. By using real-time RT-PCR, we determined the expression of IDO-2 in commercially available HepG2 cells and in three patient derived xenograft (PDX)-derived HB cell lines (HB214, HB279, HB 303) (high risk metastatic, high-risk non metastatic and-low risk, respectively). IDO-2 is expressed in both HepG2 cells and in the 3 PDX-derived cell lines. Data analysis by using linear mixed effects modelling followed by t-tests to examine specific comparisons showed significant differences between cell lines. Expression of IDO-2 in cells from the metastatic tumor (HB214) was significantly higher than in HepG2 and cells from non-metastatic disease (p&amp;lt;0.05). In conclusion, we report here for the first time that IDO-2 is expressed in HB cells. Although further investigation should be conducted in order to understand its specific role in HB, the findings in this work suggest that IDO-2 expression might be related with clinical tumor behavior. Citation Format: Lisandro Luques, Ashby Kissoondoyal, Emily De Sousa, Paula Quaglietta, David Malkin, Stefano Cairo, Emilie Indersie, Reto Baertschiger. Indoleamine-2,3-dioxygenase 2 (IDO-2) is expressed in hepatoblastoma cells and associated with metastatic state. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3539.